The therapeutic effect of anticancer agents that have been developed so far is not sufficient and the probability of curing a cancer is very low. As a cause thereof, the inability of conventional therapeutic agents to selectively target cells that form the basis of cancer tissue can be cited. In recent years, as such ‘cells forming the basis of cancer tissue’ the presence of cancer stem cells has been reported. Cancer stem cells are thought to be causal cells involved in the occurrence, recurrence, and metastasis of a cancer and, therefore, if cancer stem cells can be targeted, it can be expected that the possibility of suppressing effectively the proliferation, recurrence, and metastasis of a cancer will be high. That is, the development of a technique for detecting cancer stem cells and a novel therapeutic agent that targets cancer stem cells are important issues in cancer medicine.
On the other hand, in the elimination of tumor cells and virus-infected cells, etc. in a living body, cell-mediated immunity, in particular involving cytotoxic T cells (CTLs), plays an important role. In the case of the elimination of tumor cells, a CTL recognizes a complex of an antigen peptide (tumor antigen peptide) and a major histocompatibility complex (MHC: Major Histocompatibility Complex) class I antigen (called an HLA class I antigen in the case of humans) on a tumor cell and attacks and destroys the tumor cell. That is, a tumor antigen peptide is produced by intracellular degradation by a protease of a tumor-specific protein, that is, a tumor antigen protein, after it has been synthesized in the cell. The tumor antigen peptide thus produced binds to an MHC class I antigen (HLA class I antigen) in the endoplasmic reticulum to form a complex, which is transported to the cell surface and is presented as an antigen. A tumor-specific CTL recognizes the complex involved in this antigen presentation, and an anti-tumor effect is exhibited via cytotoxic action, lymphokine production, etc. Accompanying the elucidation of such a series of actions, therapies in which a tumor antigen protein or a tumor antigen peptide is utilized as a so-called cancer immunotherapy agent (cancer vaccine) to thus enhance cancer-specific CTLs in the body of a cancer patient are in the process of being developed.
Among them, the development of a novel cancer vaccine that can immunologically eliminate cancer stem cells has been particularly desired (e.g. Patent Document 1).
Ankyrin repeat and SOCS box-containing 4 (ASB4) is one of the genes originally identified in the process of imprinting gene screening, but in recent years it has also been identified as a gene involved in reprogramming, and it is known that its expression is not observed except for the testes of specific differentiation stage in human normal tissues. As events related to ASB4 and cancer, it has been reported that ASB4 is expressed in hepatoma cells and that the expression of ASB4 gene positively correlates with tumor invasiveness (for example, Non-Patent Documents 1 to 4).